Lung cancer is one of the most common types of human cancers. Among lung cancer patients, non-small cell lung cancer (NSCLC) accounts for 80-85% of the cancer population. Due to its high malignancy and rapid tumor development, non-small cell lung cancer when discovered and diagnosed, typically in 30-40% patient cases, has already developed into an advanced stage and missed the optimal time for surgical treatment. For those types of the patients, chemotherapy becomes all but the only option to manage the disease.
Taxane is a class of antitumor drugs widely used for chemotherapy. Docetaxel, a member of taxane, binds to intracellular free tubulin and promote the assembly of free tubulin to form stable polymeric microtubules. At the same time, docetaxel can inhibit the polymerization of microtubules depolymerization, thus breaking the dynamic equilibrium between polymerization and depolymerization of the intracellular microtubule of. Because docetaxel can inhibit cell mitosis by impacting spindle formation during mitosis, cells treated with docetaxel cannot divide and proliferate normally. Docetaxel is a semi-synthetic analogue of paclitaxel. Compared with paclitaxel, docetaxel has a higher antitumor activity and has been widely used as a first-line or second-line treatment for non-small cell lung cancer (Lin et al., China Cancer, 2008, 17(4):326-327. doi: 10.3969/j.issn.1004-0242.2008.04.019). However, the current clinical use of chemotherapy drugs including docetaxel for non-small cell lung cancer suffers from low efficiency. According to Cancer statistics (Siegel R L, Miller K D, Jemal A. CA Cancer J Clin. 2015, 65(1):5-29. doi: 10.3322/caac.21254), only 20-30% of patients responded, while non-small cell lung cancer is seen prone to metastasis and easy to relapse in treated patients.
Clearly, there is an urgent need to develop an effective therapy for non-small cell lung cancer as the current clinical application of chemotherapy drugs has not met the needs for treatment.
In recent years, it has been confirmed by a number of studies that natural substances extracted from plants have strong anti-tumor activities. It has been reported that nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone) can block the cell cycle in the G1 phase and the cell apoptosis (Qiu P, Dong P, Guan H, Li S, Ho C T, Pan M H, McClements D J, Xiao H. Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells. Mol Nutr Food Res. 2010, Suppl 2:S244-52. doi: 10.1002/mnfr.200900605).
It is thus of high utility to explore nobiletin, its analogs, or its derivatives for treating cancer including non-small cell lung cancer.